Chemokines enhance immunity by guiding naive CD8+ T cells to sites of CD4+ T cell-dendritic cell interaction.
Castellino, Flora 1*+; Huang, Alex Y. 1*; Altan-Bonnet, Gregoire 1+; Stoll, Sabine 1+; Scheinecker, Clemens 1+; Germain, Ronald N. 1
[Article] Nature. 440(7086):890-895, April 13, 2006.

(Format: HTML, PDF)

CD8 T cells have a crucial role in resistance to pathogens and can kill malignant cells; however, some critical functions of these lymphocytes depend on helper activity provided by a distinct population of CD4 T cells. Cooperation between these lymphocyte subsets involves recognition of antigens co-presented by the same dendritic cell, but the frequencies of such antigen-bearing cells early in an infection and of the relevant naive T cells are both low. This suggests that an active mechanism facilitates the necessary cell-cell associations. Here we demonstrate that after immunization but before antigen recognition, naive CD8 T cells in immunogen-draining lymph nodes upregulate the chemokine receptor CCR5, permitting these cells to be attracted to sites of antigen-specific dendritic cell-CD4 T cell interaction where the cognate chemokines CCL3 and CCL4 (also known as MIP-1[alpha] and MIP-1[beta]) are produced. Interference with this actively guided recruitment markedly reduces the ability of CD4 T cells to promote memory CD8 T-cell generation, indicating that an orchestrated series of differentiation events drives nonrandom cell-cell interactions within lymph nodes, optimizing CD8 T-cell immune responses involving the few antigen-specific precursors present in the naive repertoire.

(C) 2006 Nature Publishing Group